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Biomedical subjects

L Mathiesen

Publications and source records attributed to L Mathiesen.

At least 55 records · Page 3Linked to original sources

Prevention of Pneumocystis carinii pneumonia relapse by aerosolised pentamidine, 60 mg biweekly, using an Acorn System 22 nebuliser.

The effectiveness of biweekly administration of 60 mg aerosolised pentamidine (AP) as secondary prophylaxis against relapse of Pneumocystis carinii pneumonia (PCP) was investigated in 45 male AIDS patients. The nebuliser used was an Acorn System 22. In total the patients received AP for a mean period of 13.8 months (3.4-28.8). Six episodes of recurrent PCP were recorded. Relapse per full year of treatment on AP was 12%.

Acquired Immunodeficiency Syndrome↗

HIV-induced immunodeficiency. Relatively preserved phytohemagglutinin as opposed to decreased pokeweed mitogen responses may be due to possibly preserved responses via CD2/phytohemagglutinin pathway.

We studied the proliferative response of PBL to the mitogens PHA and PWM and Candida albicans Ag in 301 HIV seropositive homosexual men, of whom 55 had AIDS. The responses to PHA were reduced only in the clinically ill HIV seropositive subjects. In contrast, the responses to PWM were profoundly reduced in most HIV seropositive subjects including the asymptomatic group. Further analysis of 16 HIV seropositive subjects showed that the proliferative responses were reduced in both CD4 and CD8 T cell subsets. A total of 15 HIV seropositive individuals with low responses to PWM, of whom seven had AIDS and eight controls were chosen for the following studies. Expression of T3, Ti, delta receptors, and CD2 was investigated and showed an increased percentage of CD2 receptors positive cells in HIV seropositive subjects without AIDS. The proliferative responses of PBL to stimulation with PHA, PWM, antibodies to CD3, or antibodies to CD2 were investigated and showed significant correlation in controls, whereas in contrast, only the responses to PHA and CD2ab correlated in patients with AIDS. The proliferative responses to CD2ab and CD3ab in controls were larger than the responses to both PHA and PWM. In patients, these responses were less suppressed than the responses to PWM indicating that stimulation with mitogens is more complex than a simple stimulation of Ti/T3 and CD2 receptors. Further investigations were done on resting T cells, i.e., lymphocytes depleted of macrophages and pre-activated cells. Addition of PHA to these cells resulted in preactivation with expression of IL-2R (CD25) but not in proliferation. In contrast, addition of PHA plus SRBC, which bind to the CD2 receptors caused IL-2R expression, IL-2 production, and proliferation. Addition of PWM + SRBC did not result in proliferation. A comparison of the responses to PHA + SRBC of resting T cells from 26 HIV seropositive individuals, of whom seven had AIDS and 12 seronegative controls, showed that these responses were normal or only slightly decreased in the 19 seropositive men without AIDS whereas it was decreased in AIDS patients. Nevertheless, all AIDS patients showed clear-cut responses in this assay. Thus, the discrepancy between responses to PHA and PWM may be explained by an at least partially preserved function of the PHA/CD2-dependent pathway. We suggest that the defect induced by the HIV infection primarily concerns T3/Ti-induced responses.

Acquired Immunodeficiency Syndrome↗

Antibodies against the major core protein p24 of human immunodeficiency virus: relation to immunological, clinical and prognostic findings.

In 79 homosexual men positive for antibody to human immunodeficiency virus (HIV), the titer and avidity of p24 antibody was determined by an indirect ELISA and the serum tested for the presence of HIV antigen. Results were examined for a possible correlation with clinical, immunological and prognostic findings. High titers and low avidity of p24 antibodies correlated significantly with a normal pokeweed mitogen response, early lymph node changes, and an asymptomatic and stable clinical condition. In HIV antigen negative patients, low titers and high avidity of p24 antibodies correlated significantly with a progressive clinical condition. The finding of primarily high avidity antibodies against p24 antigen in patients with more advanced immunodeficiency indicates that a decline of p24 antibodies during the clinical course of HIV infection may not be explained exclusively by an increased production of viral proteins.

Acquired Immunodeficiency Syndrome↗

Suppression of p24 antigen in sera from HIV-infected individuals with low-dose alpha-interferon and zidovudine: a pilot study.

On the basis of the observations that HIV antigenaemia indicates a high risk of progression to AIDS and that zidovudine and alpha-interferon act synergistically against HIV replication in vitro, we performed a pilot trial including 12 HIV-infected asymptomatic patients with detectable p24 antigen in serum. The patients received low-dose lymphoblastoid alpha-interferon alone for 4 weeks followed by a combination of interferon and low-dose zidovudine for a further 16 weeks. The median p24 antigen level decreased significantly (P less than 0.01), the decrease being most pronounced at week 5. Decreases in haemoglobin and neutrophil counts were observed. Four patients required reduction of the zidovudine dose and three patients were transfused. In conclusion, the drug combination was capable of reducing the serum level of HIV p24 antigen and it was tolerated by the patients. Further studies are required to evaluate the clinical implications of these observations.

Acquired Immunodeficiency Syndrome↗

Humoral and cellular responses to Pneumocystis carinii, CMV, and herpes simplex in patients with AIDS and in controls.

The titers of IgG and IgA to Pneumocystis carinii in 36 AIDS patients did not differ significantly from those in 31 controls. Only 2/15 patients (13%) with P. carinii pneumonia (PCP) had titers of IgM antibodies greater than or equal to 5, which is significantly less frequent than in 32 controls (62%) and in 21 AIDS patients without PCP (43%). The risk of PCP was 5 times higher in patients without IgM antibodies to P. carinii than in patients who had these antibodies. A significantly higher percentage of those without PCP (57%) showed increasing titers of IgM antibodies to P. carinii in the second of paired samples taken about 6 months apart, compared with whose with PCP (9%; p = 0.05). All patients had high titers of antibodies to CMV and HSV and normal total concentrations of immunoglobulins. None of the patients responded in lymphocyte transformation to P. carinii, CMV, or HSV antigens. There is no obvious explanation to the selective lack of IgM antibodies to P. carinii in patients with PCP. Lack of IgM antibodies may be a marker for an immunodeficiency to P. carinii.

Acquired Immunodeficiency Syndrome↗

Skin and oral mucosal changes in patients infected with human immunodeficiency virus.

During a 6-month-period, 150 patients infected with Human Immunodeficiency Virus (HIV) were repeatedly examined by dermatologists and dentists for lesions of skin and oral mucosa. The most frequently encountered diseases were: oral hairy leukoplakia (21%), dermatophytosis (including tinea unguium/tinea pedis et inguinalis) (20%), seborrheic dermatitis (19%), viral infections (10%), oral candidiasis (7%), acne vulgaris (6%), and folliculitis (5%). A variety of other manifestations were seen, with frequencies less than 5%. Herpes zoster was seen in 3% of the patients, indicating a rate of 60/1,000 per annum. The presence of seborrheic dermatitis was statistically associated with low T-helper lymphocyte count. Patients with low T-helper lymphocyte count had on average twice as many mucocutaneous lesions as patients with a normal or moderately decreased count. Any one of the manifestations seborrheic dermatitis, oral candidiasis or oral hairy leukoplakia was associated with a greater average number of additional mucocutaneous changes than seen in patients exhibiting none of these three conditions. The high proportion of HIV-infected patients with cutaneous and oral lesions underlines the importance of referring the patients to dermatologists and dentists for examination. Prospective examinations of the study population remain to elucidate the prognostic significance of mucocutaneous manifestations of HIV-infected patients.

Acquired Immunodeficiency Syndrome↗

Stages in LAV/HTLV-III lymphadenitis. I. Histological and immunohistological classification.

Lymph nodes from 40 homosexuals with persistent, generalized lymphadenopathy were studied for histological and immunohistological changes and classified into histological stages based on the progressive destruction of lymph node follicles in association with progression of the disease. Three patterns were recognized: stage I was characterized by follicular hyperplasia, mantle zone depletion, and follicular fragmentation in the absence of vasculitis, stage II by signs of follicular involution, and stage III by depletion of follicles and dendritic reticulum cells with development of diffuse pattern. The T zone was gradually depleted of CD4-positive lymphocytes, but on further progression, lymphocytic depletion (which also involved the CD8-positive cells) and fibrosis prevailed. The 40 lymph nodes from homosexuals were classified as stage I in 18 cases, stage II in 11, and stage III in 10. One case did not fulfil our histological criteria for LAV/HTLV-III lymphadenitis, although this patient was seropositive. Convincing correlation was found between histological stages and clinical and laboratory data. The triad of follicular hyperplasia, mantle zone depletion, and follicular fragmentation, in the absence of vasculitis, appears pathognomonic for the early disease. The diffuse pattern, however, may be seen in different disease entities.

Acquired Immunodeficiency Syndrome↗

Stages in LAV/HTLV-III lymphadenitis. II. Correlation with clinical and immunological findings.

The aim of the present study was to investigate the relation between the histopathological findings in LAV/HTLV-III lymphadenitis and immunological, clinical, and serological variables. The study group included 38 consecutive homosexual men with persistent generalized lymphadenopathy (PGL) in whom lymph node biopsy was performed. The histopathological lymph node changes were grouped into three stages. Opportunistic infections at the time of biopsy and their development during follow-up were significantly associated with stage III histology (follicular depletion). Analysis of blood from 10 patients with stage III histology revealed significantly (P less than 0.01) decreased proliferative responses of lymphocytes to mitogens and reduced absolute number of CD5+ and CD4+ lymphocytes compared with 17 patients with stage I histology (follicular hyperplasia), whereas patients with stage II histology (follicular involution) had intermediate values. The absolute number of CD8+ lymphocytes was increased in all three stages, as was IgG, while increase in IgM and IgA was restricted to stage III. No difference was observed between the different histopathological stages with respect to the specificity of the anti-LAV/HTLV-III antibody as measured by immunoblotting. In conclusion, the defects of lymphocytes from the blood of LAV/HTLV-III infected persons reflect alterations in secondary lymphoid tissue. Further, there is a close correlation between these alterations and the clinical status of the patients.

Acquired Immunodeficiency Syndrome↗

Cytotoxic capabilities of lymphocytes from patients with the acquired immunodeficiency syndrome.

Lymphocytes from 16 AIDS patients were tested in the cell-mediated lympholysis assay (CML). The ability to produce alloreactive cytotoxic lymphocytes in vitro was found to be substantially reduced when compared with concomitantly investigated normal controls. Addition of interleukin 2 (IL-2) to the inducer cultures increased the cytotoxic activity, but not to normal levels. The CML response did not correlate with the relative or absolute number of Leu 3+ cells or the proliferation in effector suspensions. The ability to produce cytotoxic cells in CML, and the degree of potentiation by IL-2, was positively correlated with the absolute number of Leu 2+ cells in peripheral blood of the patients, which was below normal in 56% of the patients. It is suggested that the low CML in AIDS patients is primarily caused by defective T-cell help. In addition patients with decreased absolute numbers of Leu 2+ cells may have a reduced number of CTL precursors. The natural killer (NK) activity of AIDS lymphocytes was reduced, but could be improved by incubation with IL-2 in vitro. The mononuclear cells from the patients showed a decreased ability to respond and to stimulate in the mixed lymphocyte culture. In one of the AIDS patients, the CML was found to induce autoreactivity in vitro.

Acquired Immunodeficiency Syndrome↗

The acquired immunodeficiency syndrome (AIDS) in Denmark. A report from the Copenhagen study group of AIDS on the first 20 Danish patients.

Twenty Danish patients with the acquired immunodeficiency syndrome (AIDS) had been diagnosed by January 1984, 14 of them after 1982. Eighteen patients were male homosexuals, 8 of whom had visited the USA after 1979, 2 were heterosexual males with a history of sexual contacts in Central Africa, suggesting a transmission of AIDS from woman to man. AIDS has not been observed in drug abusers, hemophiliacs or transfused non-risk persons in Denmark. The clinical picture varied according to the presence of Kaposi sarcoma or the type of opportunistic infections, but was in general similar to that reported from the USA. Investigation of T-lymphocyte subsets revealed that the AIDS patients differed from controls and healthy homosexual men by having either a very low number of helper cells or a low helper/suppressor cell ratio. Functional immunological studies revealed a decreased natural killer cell activity and decreased blast transformation by mitogens. The survival two years after diagnosis was 16%.

Acquired Immunodeficiency Syndrome↗

Increased risk of infection with hepatitis A and B viruses in men with a history of syphilis: relation to sexual contacts.

Serum samples from 269 men with at least one episode of syphilis were tested for the presence of markers of hepatitis A and B viruses. The patients were divided into three groups: 177 homosexual men, 35 heterosexual men, and 57 men with unknown sexual contacts. The incidence of hepatitis B surface antigen or its antibody (anti-HBs) was three times greater in the homosexual men (67%) than in the men with unknown sexual contacts (25%) and the heterosexual men (23%). The incidence of anti-HBs increased with age, reaching 84% in the homosexual men 40-49 years of age. A positive correlation was found between the presence of markers of hepatitis A and B viruses and the number of episodes of syphilis in younger homosexual men (P less than 0.01). Antibody to hepatitis A virus was found in 36% of the homosexual men, 18% of the men with unknown sexual contacts, and 20% of the heterosexual men. Only one patient was found to have IgM antibodies to hepatitis A virus.

Adolescent↗

Hepatitis B and A virus antibodies in alcoholic steatosis and cirrhosis.

Sera from 74 alcoholics with cirrhosis and 63 alcoholics with steatosis were tested for antibody to hepatitis B surface antigen, to hepatitis B core antigen, and to hepatitis A virus by radioimmunoassay or enzyme-linked immunosorbent assay. No significant difference between the two groups of alcoholics could be found concerning the prevalence of these antibodies. The total group of patients had antibody to hepatitis B surface antigen or hepatitis B core antigen, or both, significantly (p less than 0.001) more often (26%) than sex- and age-matched controls (4%). No significant difference was found between patients and controls concerning the prevalence of antibody to hepatitis A virus (46% v 40%). In patients with cirrhosis, no correlation between wedged hepatic vein pressure or wedged-to-free hepatic vein pressure and any of the viral antibodies could be established. The present results suggest that hepatitis B virus does not play a major role in the progression of alcoholic liver disease, but longitudinal studies are needed to solve this problem. The reason for the increased prevalence of antibodies to hepatitis B virus in these patients is unknown.

Adult↗

Viral hepatitis in southeast Asian refugees.

Five hundred sixty-four Vietnam refugees were studied for past or present infection with hepatitis A and B virus (HAV and HBV) by sensitive serological assays for hepatitis B surface and e-antigen and antibodies to HBsAg, HBeAg, HBcAg, and HAV. Fifteen percent of the men and 6% of the women were HBsAg-positive. Of these 66% were also positive for HBeAg. Serum transaminase values did not effectively differentiate between the infectious HBeAg carriers and the less infectious anti-HBe carriers. The HBsAg carrier rate did not increase by age after infancy, and among children, carriers clustered around HBsAg carrier mothers only. In contrast, the distribution of antibodies to the three HBV-associated antigens suggested continuous exposure throughout childhood, and a 90% prevalence rate was found at the age of 20 years. Screening for HBeAg in this new population group is necessary if appropriate precautions are to be taken, and if medical management of these patients is to be optimal. The prevalence of antibody to hepatitis A increases with age to 90% at 15 years. Among anti-HAV-positive children and adults IgM- anti-HAV was found in 8% of the children and none of the adults, indicating that only a few children may be in an infectious stage at the time of study, and therefore no specific prophylactic precautions are necessary.

Adolescent↗

An epidemic of acute viral hepatitis in male homosexuals. Etiology and clinical characteristics.

Among 130 male patients admitted during a 30-month period with acute hepatitis in the Copenhagen Clinic for Infectious Diseases, 31 were homosexuals. Hepatitis B virus occurred in an endemic fashion in the homosexual subpopulation while hepatitis A infection caused a small epidemic among homosexuals during the winter 1977-78. The course of these infections showed no serological or clinical differences from the findings in 38 heterosexual male patients seen during the same period.

Hepatitis, Viral, Human↗

Enzyme-linked immunosorbent assay for detection of poliovirus antigen and antibody.

A sensitive method is described to detect poliovirus antigen in diluted samples of semi-processed and processed Salk vaccine material using a double antibody sandwich enzyme-linked immunosorbent assay (ELISA). The introduction of a simple conjugate-blocking step permits confirmation of antigen specificity and allows evaluation of neutralising antibody concentration in the sera employed as soon as four hours after sample addition.

Antibodies, Viral↗